Dataset Information

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis.

ABSTRACT:

Importance

Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described.

Objective

To systematically assess the risk of adverse events after high-dose supplementation with vitamin D reported in published randomized clinical trials.

Data sources

PubMed and ClinicalTrials.gov were searched through August 24, 2021.

Study selection

Randomized clinical trials of high-dose vitamin D supplementation in children aged 0 to 6 years, defined as greater than 1000 IU/d for infants (aged 0-1 year) and greater than 2000 IU/d for children aged 1 to 6 years.

Data extraction and synthesis

Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 reviewers independently extracted the data from the eligible studies. Summary risk ratio (RR), 95% CI, and P values were derived from random-effects meta-analysis.

Main outcomes and measures

Adverse events, serious adverse events (SAEs), and/or levels of 25-hydroxyvitamin D, calcium, alkaline phosphatase, phosphate, parathyroid hormone, and/or the ratio of urine calcium to creatinine levels.

Results

A total of 32 randomized clinical trials with 8400 unique participants were included. Different clinical outcomes of children receiving high-dose vitamin D supplements ranging from 1200 to 10 000 IU/d and bolus doses from 30 000 IU/week to a single dose of 600 000 IU were evaluated. Eight studies with 4612 participants were eligible for meta-analysis using a control group receiving either low-dose vitamin D supplementation (≤400 IU/d) or placebo when investigating the risk of SAEs such as hospitalization or death. No overall increased risk of SAEs in the high-dose vitamin D vs control groups was found (RR, 1.01 [95% CI, 0.73-1.39]; P = .89, I2 = 0%). In addition, risk of hypercalcemia (n = 726) was not increased (RR, 1.18 [95% CI, 0.72-1.93]; P = .51). Clinical adverse events potentially related to the vitamin D supplementation reported in the studies were rare.

Conclusions and relevance

This meta-analysis and systematic review found that high-dose vitamin D supplementation was not associated with an increased risk of SAEs in children aged 0 to 6 years, and that clinical adverse events potentially related to the supplementation were rare. These findings suggest that vitamin D supplementation in the dose ranges of 1200 to 10 000 IU/d and bolus doses to 600 000 IU to young children may be well tolerated.

SUBMITTER: Brustad N

PROVIDER: S-EPMC9011124 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis.

Brustad Nicklas N Yousef Sina S Stokholm Jakob J Bønnelykke Klaus K Bisgaard Hans H Chawes Bo Lund BL

JAMA network open 20220401 4

<h4>Importance</h4>Several health benefits of vitamin D have been suggested; however, the safety of high-dose supplementation in early childhood is not well described.<h4>Objective</h4>To systematically assess the risk of adverse events after high-dose supplementation with vitamin D reported in published randomized clinical trials.<h4>Data sources</h4>PubMed and ClinicalTrials.gov were searched through August 24, 2021.<h4>Study selection</h4>Randomized clinical trials of high-dose vitamin D supp ...[more]

PMID: 35420658

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Project description:ContextVitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive.ObjectiveThe aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age.Data sourcesPubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria.Data extractionMeta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included.Data analysisSeven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62-1.10). There was a 57% (95%CI, 0.30-0.61), 56% (95%CI, 0.27-0.07), and 59% (95%CI, 0.26-0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality.ConclusionHigh-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed.Systematic review registrationPROSPERO registration number CRD42022355206.

Project description:Zinc supplementation reduces morbidity, but evidence suggests that excessive intakes can have negative health consequences. Current guidelines of upper limits (ULs) of zinc intake for young children are extrapolated from adult data. This systematic review (PROSPERO; registration no. CRD42020215187) aimed to determine the levels of zinc intake at which adverse effects are observed in young children. Studies reporting potential adverse effects of zinc intake in children aged 0-3 y were identified (from inception to August 2020) in MEDLINE, Embase, and the Cochrane Library, with no limits on study design. Adverse clinical and physical effects of zinc intake were synthesized narratively, and meta-analyses of biochemical outcomes were conducted. Random effects models were used to generate forest plots to examine the evidence by age category, dose, dose duration, chemical formula of zinc, and zinc compared with placebo. The Joanna Briggs Institute Critical Appraisal Checklist, Cochrane Risk of Bias 2, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline were employed to assess risk of bias and to appraise the certainty of evidence. Fifty-eight studies assessed possible adverse effects of zinc doses ranging from 3 to 70 mg/d. Data from 39 studies contributed to meta-analyses. Zinc supplementation had an adverse effect on serum ferritin, plasma/serum copper concentration, serum transferrin receptor, hemoglobin, hematocrit, and the odds of anemia in ≥1 of the subgroups investigated. Lactulose:mannitol ratio was improved with zinc supplementation, and no significant effect was observed on C-reactive protein, erythrocyte superoxide dismutase, zinc protoporphyrin, blood cholesterol, and iron deficiency anemia. The certainty of the evidence, as assessed using GRADE, was very low to moderate. Although possible adverse effects of zinc supplementation were observed in some subgroups, it is unclear whether these findings are clinically important. The synthesized data can be used to undertake a dose-response analysis to update current guidelines of ULs of zinc intake for young children.

Project description:BackgroundVitamin D deficiency has been highlighted as a serious public health problem in the United Kingdom. One in four toddlers are not achieving the recommended intake for their healthy development. This study uses quantitative and qualitative methods to explore parents' perceptions, awareness and behaviours around vitamin D intake, and the acceptability of and factors affecting purchasing of food and drink fortified with Vitamin D in children aged 0-2 years old.MethodsOne hundred and ninety-four parents completed an online questionnaire, advertised to parents with one child aged up to 2 years on popular social media websites. The majority of participants were mothers, White-British ethnic background, aged 25-44 years. Participants provided an email address if they wanted to be contacted about the focus groups. Recruitment posters advertising the focus groups were placed in community centres. Eighteen participated in 5 focus groups (13 parents), and 5 individual interviews. A thematic analysis methodology was applied.ResultsFifty-seven percent (n = 110) of parents reported receiving information about vitamin D during pregnancy and 52% (n = 100) after the birth of their child. Parents reported a low level of satisfaction with vitamin D information: many thought it was limited and recommendations on supplements were unclear. Parents wanted more information about vitamin D requirements for their child (80%, n = 153 out of 192 respondents, 2 non-response), about vitamin D and breastfeeding (56%, n = 108) and vitamin D and pregnancy (49%, n = 94). The recommendations were for simpler, easier to read, with specific and clearer guidelines; delivered regularly during routine appointments, at timely stages throughout pregnancy and after the birth. 23% (n = 45, out of 194 respondents) of parents did not know why vitamin D is important for health. Only 26% (n = 49, out of 192 respondents) of parents reported giving their youngest child a vitamin D supplement on most days of the week. The majority of parents (interview/focus group) wanted more information about foods/drinks fortified with vitamin D.ConclusionParents were generally not aware of the importance of vitamin D, dietary requirements including supplementation and the availability of vitamin D fortified foods. Major improvements are required for the effective promotion of vitamin D information to parents.

Dataset Information

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis.

Importance

Objective

Data sources

Study selection

Data extraction and synthesis

Main outcomes and measures

Results

Conclusions and relevance

Publications

Safety of High-Dose Vitamin D Supplementation Among Children Aged 0 to 6 Years: A Systematic Review and Meta-analysis.

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